The long term objective of the present proposal is to identify the vasomotive substances that initiate blood flow regulation of the inner retinal vessels in the normal retina, and to determine the change in concentration of such substances that accompany exposure of the retina to elevated glucose levels. To determine whether inner retinal PO2 serves as a first stage stimulus for blood flow change, we propose simultaneous measurements of intraretinal PO2, by means of an oxygen microcathode, and retinal blood flow by means of laser Doppler velocimetry (LDV) in the eye of anesthetized cat. Using a physiologic stimulus for vasomotion, i.e., the transition from dark to light, we will explore the possibility of a causal relationship between PO2 and blood flow by determining the amplitude and phase lag of changes in PO2 and blood flow to time-varying light stimuli. Since the effect of decreased local PO2 on blood flow may be mediated by a local acidosis, we also propose simultaneous measurements of intraretinal pH, by means of a pH-sensitive microelectrode, and blood flow by LDV. The amplitude and phase lag of pH change to light will be compared to that observed in PO2 to light, to determine whether pH changes intervene between the change in PO2 and blood flow. We will also determine the effect of transient, induced hyperglycemia on intraretinal PO2, intraretinal pH, and retinal blood flow in light and dark. Moreover, we will study the effects of a maintained elevation in glucose on retinal oxygen consumption, CO2 production, and interstitial pH in the isolated neurosensory retina. In this way, we will determine whether elevated glucose causes changes in intraretinal PO2 and/or intraretinal pH sufficient to elicit vasomotion and blood flow regulation. The proposed experiments will provide information on the basic mechanisms of blood flow regulation, and will be relevant to the changes in vasomotion observed in diabetic retinopathy.